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BACKGROUND: The association of workplace factors on mental health of healthcare workers (HCWs) during the COVID-19 pandemic needs to be urgently established. This will enable governments and policy-makers to make evidence-based decisions. This international study reports the association between workplace factors and the mental health of HCWs during the pandemic. METHODS: An international, cross-sectional study was conducted in 41 countries. The primary outcome was depressive symptoms, derived from the validated Patient Health Questionnaire-2 (PHQ-2). Multivariable logistic regression identified factors associated with mental health outcomes. Inter-country differences were also evaluated. RESULTS: A total of 2527 responses were received, from 41 countries, including China (n = 1213; 48.0%), UK (n = 891; 35.3%), and USA (n = 252; 10.0%). Of all participants, 1343 (57.1%) were aged 26 to 40 years, and 2021 (80.0%) were female; 874 (34.6%) were doctors, and 1367 (54.1%) were nurses. Factors associated with an increased likelihood of depressive symptoms were: working in the UK (OR = 3.63; CI = [2.90–4.54]; p < 0.001) and USA (OR = 4.10; CI = [3.03–5.54]), p < 0.001); being female (OR = 1.74; CI = [1.42–2.13]; p < 0.001); being a nurse (OR = 1.64; CI = [1.34–2.01]; p < 0.001); and caring for a COVID-19 positive patient who subsequently died (OR = 1.20; CI = [1.01–1.43]; p = 0.040). Workplace factors associated with depressive symptoms were: redeployment to Intensive Care Unit (ICU) (OR = 1.67; CI = [1.14–2.46]; p = 0.009); redeployment with perceived unsatisfactory training (OR = 1.67; CI = [1.32–2.11]; p < 0.001); not being issued with appropriate personal protective equipment (PPE) (OR = 2.49; CI = [2.03–3.04]; p < 0.001); perceived poor workplace support within area/specialty (OR = 2.49; CI = [2.03–3.04]; p < 0.001); and perceived poor mental health support (OR = 1.63; CI = [1.38–1.92]; p < 0.001). CONCLUSION: This is the first international study, demonstrating that workplace factors, ...